A Study of Atezolizumab Administered in Combination With Bevacizumab and/or With Chemotherapy in Participants With Locally Advanced or Metastatic Solid Tumors

Conditions

• Cancer

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• 5-FU — DRUG
  Participants will receive 5-FU 400 mg/m\^2 IV q2w.
• Atezolizumab — DRUG
  Participants will receive IV atezolizumab (800 mg q2w or 1200 mg q3w) q3w.
• Bevacizumab — DRUG
  Participants will receive bevacizumab 10 mg/kg or 15 mg/kg IV q3w.
• Carboplatin — DRUG
  Participants will receive carboplatin IV q3w with target AUC of 6 mg/mL.
• Leucovorin — DRUG
  Participants will receive leucovorin 400 mg/m\^2 IV q2w.
• Nab-paclitaxel — DRUG
  Participants will receive nab-paclitaxel 100 mg/m\^2 IV qw.
• Oxaliplatin — DRUG
  Participants will receive oxaliplatin 85 mg/m\^2 IV q2w.
• Paclitaxel — DRUG
  Participants will receive paclitaxel 200 mg/m\^2 IV q3w.
• Pemetrexed — DRUG
  Participants will receive pemetrexed 500 mg/m\^2 IV q3w.

Study Details

This open-label, Phase Ib study that has six treatment arms is designed to assess the safety, pharmacology and preliminary efficacy of atezolizumab (MPDL3280A; an engineered anti-programmed death-ligand 1 \[PDL1\] antibody) administered with bevacizumab (Arm A) and with bevacizumab plus oxaliplatin, leucovorin, and 5-fluorouracil (5-FU) (FOLFOX) (Arm B), with carboplatin and paclitaxel (Arm C), with carboplatin and pemetrexed (Arm D), with carboplatin and nab-paclitaxel (Arm E), and with nab-paclitaxel (Arm F) in participants with locally advanced or metastatic solid tumors. The study includes dose escalation cohort for establishing the maximum tolerated dose (MTD) or maximum administered dose (MAD) and then expansion cohort will be initiated based on a selected dose level at or below the MTD or MAD.

Key Dates

Start date

Jul 11, 2012

Status verified

Oct 2020

Primary completion

Feb 26, 2020

Completion

Feb 26, 2020

Study Design

Enrollment

240 participants (actual)

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Experimental: A: Atezolizumab + Bevacizumab
  Participants will receive atezolizumab 10 milligrams per kilogram (mg/kg) intravenous (IV) infusion (or a selected dose level not to exceed the single agent MTD or MAD determined in Study PCD4989g) with bevacizumab 15 mg/kg every 3 weeks (q3w). After establishment of MTD or MAD, participants will receive bevacizumab 15 mg/kg IV infusion on Day 1 of Cycle 1 followed by atezolizumab 1200 mg IV infusion q3w after Days 5-7 and then atezolizumab 1200 mg q3w and bevacizumab 15 mg/kg q3w on Day 1 of all subsequent cycles until disease progression or unacceptable toxicity.
• Experimental: B: Atezolizumab + Bevacizumab + FOLFOX
  Participants will receive FOLFOX IV infusion (oxaliplatin \[85 milligrams per square meter {mg/m\^2}\], leucovorin \[400 mg/m\^2\], 5-FU \[400 mg/m\^2\]) on Day 1 of Cycle 1 and then atezolizumab 800 mg IV infusion every 2 weeks (q2w), bevacizumab 10 mg/kg IV infusion q3w and FOLFOX q2w on Day 1 of all subsequent cycles as per institutional guidelines until disease progression or unacceptable toxicity.
• Experimental: C: Atezolizumab + Carboplatin + Paclitaxel
  Participants will receive atezolizumab 1200 mg IV infusion q3w in combination with paclitaxel 200 mg/m\^2 IV infusion q3w and then carboplatin IV q3w (on Day 1 of every 3-week cycle) to achieve an initial target area under the curve (AUC) of 6 milligrams per milliliter\*minute (mg/mL\*min) until disease progression or unacceptable toxicity.
• Experimental: D: Atezolizumab + Carboplatin + Pemetrexed
  Participants will receive atezolizumab 1200 mg IV infusion q3w in combination with premetrexed 500 mg/m\^2 IV infusion q3w and then carboplatin IV q3w (on Day 1 of every 3-week cycle) to achieve an initial target AUC of 6 mg/mL\*min until disease progression or unacceptable toxicity.
• Experimental: E: Atezolizumab + Carboplatin + Nab-paclitaxel
  Participants will receive atezolizumab 1200 mg IV infusion q3w (on Day 1 of every 3-week cycle) in combination with nab-paclitaxel 100 mg/m\^2 IV infusion once weekly (qw) (on Days 1, 8 and 15 of every 3-week cycle) and then carboplatin IV infusion q3w (on Day 1 of every 3-week cycle) to achieve an initial target AUC of 6 mg/mL\*min until disease progression or unacceptable toxicity.
• Experimental: F: Atezolizumab + Nab-paclitaxel
  Participants will receive atezolizumab 800 mg IV infusion q2w (Days 1 and 15) in combination with nab-paclitaxel 125 mg/m\^2 IV infusion qw (on Days 1, 8 and 15 of every 3-week cycle) until disease progression or unacceptable toxicity.

Primary Outcome Measure

Maximum Tolerated Atezolizumab Dose [ Time Frame: Days 1-21 of Cycle 1 (Cycle length = 21 days) for Arms A, C, D and E and the 28 days following the first administration of atezolizumab in Arm B ]

Locations (11)

Find similar trials in Aurora, CO

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